Microbubbles and methods for oxygen delivery

Abstract

Compositions containing a carrier and microbubbles encapsulating one or more gases, preferably oxygen, and methods for making and using the compositions are described herein. The microbubbles contain a lipid envelope. The compositions may be administered to a patient to quickly deliver large amounts of oxygen to the patient's blood supply or directly to a tissue in need of oxygen. The compositions may be administered via injection or as a continuous infusion. The compositions contain a concentrated microbubble suspension, where the suspension contains at least 40 mL oxygen/dL suspension. The microbubbles are preferably less than 20 microns in diameter, more preferably less than 15 microns in diameter. The microbubbles described herein may be administered to a patient in an effective amount to increase in oxygen concentration in the patient's blood, and/or one or more tissues or organs.

We claim: 
     
       1. A method for delivering oxygen to a patient, comprising
 administering via injection or infusion to the patient a composition, comprising a suspension comprising microbubbles and a carrier, wherein the microbubbles comprise a lipid envelope and a gas core, wherein the gas core comprises oxygen and does not contain a fluorinated gas, wherein the lipid envelope comprises one or more lipids, wherein the lipid is a phospholipid comprising acyl chains having an average length of 10 to 24 carbons, wherein the outer surface of the lipid envelope forms a protective border, and wherein the suspension comprises at least 40% oxygen by volume, 
 wherein the patient is experiencing local or systemic hypoxia, 
 wherein the composition is administered in an effective amount to increase the concentration of oxygen in the patient's blood, tissue or organ in need of oxygen, and 
 
       wherein the microbubbles release the effective amount of oxygen within 0.5 seconds to 1 minute following administration to the patient. 
     
     
       2. The method of  claim 1 , wherein the lipid envelope is a monolayer. 
     
     
       3. The method of  claim 1 , wherein the oxygen is administered via injection. 
     
     
       4. The method of  claim 1 , wherein the hypoxic conditions arise in the patient as a result of a disease or disorder selected from the group consisting of congenital physical or physiologic diseases or disorders, embolisms, peripheral artery occlusive disease, transient ischemic attacks, strokes, acute trauma, surgical interventions, and exposure to chemical or environmental agents. 
     
     
       5. The method of  claim 1 , wherein the suspension comprises 40 to 70% oxygen by volume. 
     
     
       6. The methods of  claim 1 , wherein the composition is administered at a rate of 0.5 to 400 mL/minute. 
     
     
       7. A method for delivering oxygen to a patient, comprising
 administering via injection or infusion to the patient a composition, comprising a suspension comprising microbubbles and a carrier, wherein the microbubbles comprise a lipid envelope and a gas core, wherein the gas core comprises oxygen and does not contain a fluorinated gas, wherein the lipid envelope comprises one or more lipids, wherein the lipid is a saturated diacyl phosphatidylcholine having the formula Di-C n -PC, where n is between 12 and 24, wherein the outer surface of the lipid envelope forms a protective border, and wherein the suspension comprises at least 40% oxygen by volume, 
 wherein the patient is experiencing local or systemic hypoxia, 
 wherein the composition is administered in an effective amount to increase the concentration of oxygen in the patient's blood, tissue or organ in need of oxygen, and 
 
       wherein the microbubbles release the effective amount of oxygen within 0.5 seconds to 1 minute following administration to the patient. 
     
     
       8. The method of  claim 7 , wherein the lipid is a saturated diacyl phosphatidylcholine having the formula Di-C n -PC, where n is 16 or 18. 
     
     
       9. The method of  claim 1 , wherein the microbubbles are stable at 4° C. and standard pressures for weeks to months. 
     
     
       10. The method of  claim 7 , wherein the lipid envelope further comprises a sterol. 
     
     
       11. The method of  claim 1 , wherein the amount of oxygen that is released is effective to raise the oxygen content of circulating blood. 
     
     
       12. The method of  claim 11 , wherein the amount of oxygen that is released is effective to restore PO 2  levels to normal levels. 
     
     
       13. The method of  claim 11 , wherein the amount of oxygen that is released is effective to resuscitate the patient's heart. 
     
     
       14. The method of  claim 1 , wherein the oxygen is administered as a continuous infusion.